Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort
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Colorectal neoplasmRisk factorsWorld Cancer Research Fund/American Institute for Cancer Research RecommendationsTargeted metabolomics
Joseph A. Rothwell... [et al.]. Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort, Clinical Gastroenterology and Hepatology, Volume 20, Issue 5, 2022, Pages e1061-e1082, ISSN 1542-3565, [https://doi.org/10.1016/j.cgh.2020.11.045]
SponsorshipWorld Cancer Research Fund International (WCRF) 20131002; European Commission grant EU-FP7/BBMRI-LPC 313010; International Agency for Research on Cancer; Danish Cancer Society; Ligue Contre le Cancer (France); General Electric; Institut Gustave-Roussy (France); Mutuelle Generale de l'Education Nationale (France); Institut National de la Sante et de la Recherche Medicale (Inserm); Deutsche Krebshilfe German Cancer Research Center (Germany) Federal Ministry of Education & Research (BMBF) Deutsche Krebshilfe; Hellenic Health Foundation (Greece); Fondazione AIRC per la ricerca sul cancro; Consiglio Nazionale delle Ricerche (CNR); Dutch Ministry of Public Health, Welfare and Sports (The Netherlands) Netherlands Cancer Registry (The Netherlands) Netherlands Government; Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway); Instituto de Salud Carlos III PI13/00061 PI13/01162; Junta de Andalucia; Basque Government; Regional Government of Murcia; Regional Government of Navarra; Instituto de Salud Carlos III Cooperative Research in Health (Spain) RD06/0020; Swedish Cancer Society Swedish Research Council; County Council of Skane (Sweden) County Council of Vasterbotten (Sweden); Cancer Research UK 14136 C570/A16491 C8221/A19170; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 1000143 MR/M012190/1
BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/ American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1–5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29–0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50–0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86–1.00) overall. Signature associations were stronger in male compared with female participants. CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.